In every normal adult, blood cells are produced at the bone marrow from stem cells through a process called “hematopoiesis”. After several steps of proliferation and differentiation, those progenitor pluripotent cells are capable of autoduplicating without differentiating themselves (endoduplication/autoreplication) or capable of generating a series of progenitor cells grouped in 4 principal ways of differentiation: a) erythroid (red blood cells or erythrocytes); b) myeloid (polimorphonuclear leucocytes and monocytes); c) lymphoid (lymphocytes) and d) megakaryiotic (generator of megakaryocytes/platelets). The quantity and cellular type produced by the bone marrow is a process finely regulated by a complex network of cytokines or growth factors that act via membrane-bound receptors on the target cells. These cytokines include a heterogeneous group of growth factors including interleukins (among others TNF-α, IL-3, IL-6, IL-8 e IL-11) and glycoproteic hormones called “Colony Stimulating Factors” (Granulocyte Colony stimulating factors and Granulocyte/Macrophage Colony stimulating factors [G-CSF y GM-CSF respectively]); Erythropoietin as stimulation factor of erythrocyte progenitors and Thrombopoietin as stimulator of platelet progenitors.
An increased knowledge of hematopoiesis and its regulation has lead to the use of diverse hematopoietic cytokines in medical treatment. In this way, medical treatments have been included based on:                Erythropoietin (EPO) for the treatment of secondary anemia in chronic kidney failure.        Colony stimulating factors (G-CSF y GM-CSF) to accelerate the recovery of the immune system in cancer patients undergoing chemotherapy or those receiving a bone marrow transplant.        IL-2 and Interferon-α Both have been widely used in conjunction with chemotherapeutic agents. Interferons are being used, with certain success, in the treatment of chronic hepatitis, as well as IL-2 in AIDS associated to antiretroviral agents.        
The circulating blood platelets are produced in the bone marrow and play a crucial role in blood coagulation. Platelets adhere to sites of tissue damage and recruit others to aggregate with it to form the “primary hemostatic plug”. In addition, it serves as the surface upon which the coagulation factors are activated to produce a fibrin clot. In the absence of platelets, both of these functions are deficient and bleeding ensues (1). The generation of platelets implies proliferation and differentiation of bone marrow stem cells, into megakaryocytic cells which will generate the mature platelets (thrombocytes) that normally circulate in peripheral blood.
The physiological process by which platelets are generated requires the presence of factors called “Thrombocytopoietic” as growth and development factors from the megakaryocytic-lineage. In clinical medicine, the decrease of the number of platelets (thrombocytopenia) is a great complication related to two relevant situations: a) diseases that affect the normal generation of platelets (primary thrombocytopenia) and B) as a result of complications derived form therapeutic treatment in cancer patients or patients that have received a bone marrow transplant (secondary thrombocytopenia). The increased risk of hemorrhages in these patients actually requires the administration of platelet concentrates from normal donors with the associated biological risk (allergies, infections, immune hypersensitivity). From the early description in 1958, of a thrombopoietin activity in thrombocytopenic animals by Kelemen and cols. (2), we had to wait until 1994 in order to identify that factor, that was purified and cloned by several groups, as a glycoprotein capable of binding the cellular receptor Mpl (oncogene responsible of the murine myeloproliferative leukemia virus) (3) that was identified as Thrombopoietin (alternatively called: c-Mpl ligand; Megapoietin or Megakaryocyte Growth and Development Factor (MGDF)) able to specifically stimulate the megakaryocytopoiesis or thrombocytopoiesis (4-8). Other factors with thrombocytopoietic activity have been described (9), including IL-6 and IL-11 although they are not specific and have pleiothropic actions. The administration of high doses of IL-11 and IL-6 isolatedly, have resulted in low increments of circulating platelets (10) The gene of Human Thrombopoietin (hTPO) has been localized as a single copy, to chromosome 3 (3q26-27). It codifies for a protein of 353 amino acids (open reading frame of 10590 base pairs), including a signal peptide of 21 amino acids (aa) (63 base pairs). The mature protein has 332 aa (996 bp) and an estimated molecular weight of 38 kDa (not glycosilated). It has 6 N-glycosilation sites in order to generate a complete glycosilated protein of 70-80 kDa and a cleavage site, between arginines 153 and 154, where the protein is divided into two domains: a) a highly glycosilated c-terminal domain without homology with known proteins, and b) an EPO-like or N-terminal domain of 153 aa with 23% of identity with EPO. Allowing for conservative aa substitutions, sequence conservation approaches 50%. It is important to highlight that the non-glycosilated form has complete activity in vitro but not in vivo due to a decreased stability and a quick depuration in the circulation. Besides the native molecule (70-80 kDa), several forms of circulating TPO have been described, as a result of its partial proteolysis consisting of forms of 30,25 and 18 kDa, all truncated at the C-terminal domain (9, 11 and 12).
At present, the only factor with thrombocytopoietic activity available and approved by the FDA (Food and Drug Administration) is the human recombinant IL-11.